This multi-phase SBIR project targets a significant problem within the mission of the National Institute of General Medical Sciences: rapid size-based purification and separation of macromolecules, including proteins, nucleic acids and polysaccharides. The main objective is to develop novel ultrafiltration membranes with unprecedented sharp and controllable molecular-weight cut-off (MWCO) and reduced fouling. Such membranes are needed to fully realize the potential benefits of ultrafiltration (UF) and thereby address various pressing needs in biochemical and medical research, medical care, bioanalysis and biomanufacturing. Synkera aims to addresses this challenge by developing and commercializing membranes made from self-organized nanoporous ceramic with practically monodisperse nanometer-scale pores. At the core of this approach, which was proven feasible in Phase I, is Synkera's unprecedented ability to precisely tune the membrane pore diameter to any value in the 0.5-150 nm range. All the key Phase I objectives have been met or exceeded. For the first time, Synkera fabricated prototypes of such membranes and demonstrated their superior performance in comparison with commercial membranes. A clear breakthrough opportunity is now open to develop a whole new family of UF membranes for a variety of applications with enormous market potential and technical, economical, and health benefits to the end users, consumers and patients. Not only do the new membranes offer a performance improvement for established UF uses, but the advanced architecture and unrivaled control of the structure of Synkera's membranes also potentially enable new breakthrough applications such as fractionation of complex macromolecule mixtures. To fully explore the potential of this technology, Synkera established collaborative R&D with several academic and industrial partners. The near-term products based on the proposed technology include planar UF filters that outperform currently available membranes, as well as application-specific membranes (e.g., for protein separation) and bioanalysis substrates (e.g., for glucose sensing). In partnership with OEM manufacturers of biomedical consumables, we will also develop and commercialize centrifuge, syringe and in-line filters, filter cartridges, multiwell-plate inserts, and UF modules. The main objective of Phase II is now to perform a systematic development of the membrane technology to meet the requirements of different applications, and advance it to a readiness level that enables inexpensive yet high-performance membranes and derivative products. PUBLIC HEALTH RELEVANCE: The project addresses a significant problem in biomedical research and medical care: rapid size-based purification and separation of macromolecules, including proteins, nucleic acids and polysaccharides. The development of novel advanced ultrafiltration membranes with unprecedented sharp and controllable molecular-weight cut-off and reduced fouling is proposed. The proposed technology will enable a novel family of high-performance membranes for use in biochemical analysis, laboratory studies, and, potentially, in hemodialysis for treatment of end-stage renal failure and in open heart surgery for blood oxygenation.